Efficacy of Brigatinib in Patients with Metastatic NSCLC − Real-World Clinical Data

Brigatinib in Targeted Treatment of NSCLC

The second-generation anaplastic lymphoma kinase (ALK) inhibitor brigatinib is approved for use in patients with previously untreated ALK-positive advanced NSCLC as well as in patients with the same diagnosis whose disease has progressed following crizotinib therapy.

In a phase II clinical trial, brigatinib achieved a median progression-free survival (PFS) of 16.7 months with a response rate of 56% and a median overall survival (OS) of 34.1 months in patients with metastatic disease pre-treated with crizotinib. Even before approval by European regulatory authorities, an early access treatment program was launched in 2016 in 9 European countries. The aim of this presented analysis was to evaluate the effectiveness of brigatinib treatment under real-world clinical conditions.

Study Methodology and Patient Population

A retrospective evaluation of medical records was performed for patients who started brigatinib treatment between June 2016 and December 2017 at oncology centers in Italy, Norway, Spain, and the United Kingdom.

The analysis included data from patients with ALK-positive metastatic NSCLC, including those with brain metastases, who were resistant or intolerant to treatment with at least one ALK inhibitor and had a performance status of ≤ 3 according to ECOG criteria. After 7 days of initiation treatment with a daily dose of 90 mg, brigatinib was administered to patients at a dose of 180 mg once daily.

The objective of the analysis was to describe patient characteristics, clinical symptoms, treatment regimens used, and their outcomes.

Results

Data from 104 patients (43% male, median age 53 years, 63% had CNS metastases) were included in the analysis. Before starting brigatinib treatment, patients had undergone an average of 2 lines of systemic therapy (37.5% of patients had at least 3 lines). 83.6% of patients had previous crizotinib treatment, 50.0% had ceritinib, 6.7% had alectinib, and 4.8% of patients were treated with lorlatinib.

Follow-up lasted for 16.5 months (median). As of the analysis date, 77 patients had discontinued brigatinib treatment, with 4 patients stopping due to adverse events. The overall response rate was 39.8% with a median PFS of 11.3 months (95% confidence interval [CI] 8.6−12.9). The median overall survival was 23.3 months (95% CI 16.0 to not reached).

After discontinuing brigatinib treatment, 53 patients continued with systemic therapy, 42 of whom were treated with an ALK inhibitor (34 with lorlatinib).

Conclusion

The presented real-world clinical data demonstrate robust activity and tolerability of brigatinib in patients with metastatic ALK-positive NSCLC who were significantly more pre-treated than participants in clinical trials.

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Source: Popat S., Brustugun O. T., Cadranel J. et al. Real-world treatment outcomes with brigatinib in patients with pretreated ALK⁺ metastatic non-small cell lung cancer. Lung Cancer 2021; 157: 9−16, doi: 10.1016/j.lungcan.2021.05.017.